个人简介

B.Sc. (Bachelor of Science) Ph.D. (Doctor of Philosophy)

研究领域

Molecular and Development Genetics

Our work focuses on two genetic networks that enable ubiquitous cellular structures, the actin and microtubule-based cytoskeletons, to carry out specific processes critical to C. elegans embryonic development. The first genetic network that we study focuses on morphogenesis - how a ball of cells (the embryo) is transformed into a tube-shaped worm. This occurs when the epidermal cells on the surface of the embryo contract, squeezing the embryo into its new shape. We found the gene let-502 (which encodes a Rho-binding kinase) and me1-11 (a myosin phosphatase) function with ten other genes to cause the actin cytoskeleton in the embryo's epidermal cells to contract. Homologous contractile pathways mediate rearrangements of the actin-myosin cytoskeleton during the cellular remodelling common to animal embryogenesis, neuronal out growth and smooth muscle contraction. The second genetic network enables the embryo to change from one mode of cell division to another, from meiosis to mitosis. The microtubule-based spindles for meiosis and mitosis are very different, but occur in the same cytoplasm within a short time of one another. This requires that the products unique to one division be carefully regulated so as not to interfere with the other division. We found that the genes mei-1 and mei-2, which encode subunits of the microtubule-severing protein “katanin”, function to keep meiotic spindle microtubules short in a cytoplasm that will soon support the unusually long microtubules characteristic of the early cleavage spindles. mei-1/mei-2 activity must be precisely confined to meiosis, otherwise lethal mitotic defects result. This is accomplished through the activity of the gene mel-26, which encodes the substrate-specific adaptor that marks mei-1 protein for ubiquitin-mediated degradation. In both projects, classical genetic methods are used to identify interacting genes and then molecular approaches are employed to clone the genes and analyze the genetic interactions at the biochemical level.

近期论文

查看导师新发文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Connolly, A.M., Osterberg, V., Christensen, S., Price, M., Lu, C., Chicas-Cruz, K., Lockery, S., Mains, P.E., and Bruce Bowerman, B. (2014) C. elegans oocyte meiotic spindle pole assembly requires microtubule severing and the calponin homology domain protein ASPM-1. Molec Biol Cell.25:1298-1311. McNally, K., Berg, E., Daniel Cortes, D., Hernandez, V., Mains, P.E. and McNally, F.J. (2014) Katanin maintains meiotic metaphase chromosome alignment and spindle structure in vivo and has multiple effects on microtubules in vitro. Molec Biol Cell. 25:1037-1049. Gomes. J.E., Tavernier, N. Richaudeau, B., Forschmester, E., Mains, P.E., Dumont, J. and Pintard, L. Temporal regulation of microtubule-severing in C.elegans embryo through dephosphorylation of MEI-1/katanin and degradation of its activiting phosphatase. J. Cell Biol., 202:431-439. Refai, O., Rohs, P., Mains, P.E. and Gaudet. J. Extension of Caenorhabditis elegans pharyngeal M1 neuron axon is regulated by multiple mechanisms. G3: Genes, Genomes, Genetics 3:2015-2029 Vanneste, C.A., Pruyne, E., E., and Mains, P.E. The role of the formin gene fhod-1 in C.elegans embronic morphogenesis. Worm 2013 e25040 Wilson, K.J., Qadota, H., Mains, P.E. and Guy M. Benian (2012) UNC-89 (obscurin) binds to MEL-26, a BTB domain protein, and affects the function of MEI-1 (katanin) instriated muscle of C. elegans. Mol.Bio.Cell, 23:2623-2634. Johnson, J.L., Lu, C., Raharjo, E., McNally, K., McNally, F.J. and Mains, P.E. (2009) Levels of the ubiquitin ligase substrate adaptor MEL-26 are inversely correlated with MEI-1/katanin microtubule-severing activity during both meiosis and mitosis. Dev. Biol. 330: 349-357. Xue, Han, Gomes, J.E., Birmingham, C.L. Pintard, L., Sugimoto, A. and Mains, P.E. (2009) The role of protein phosphatase 4 (PP4) in regulating microtubule severing in the C. elegans embryo.Genetics 181: 933-943. Luo, J., Riabowol, K. and Mains, P.E. (2009) The Caenorhabditis elegans ing-3 gene regulates ionizing radiation-induced germ cell apoptosis in a p53-associated pathway. Genetics 181: 473-482. Lu, C., and Mains, P. E. (2007). The C. elegans anaphase promoting complex and MBK-2/DYRK kinase act redundantly with CUL-3/MEL-26 ubiquitin ligase to degrade MEI-1 microtubule-severing activity after meiosis. Dev. Biol. 302: 438–447. Luke-Glaser, S., Pintard, L., Lu, C., Mains, P.E. and Peter, M. (2005) The BTB Protein MEL-26 Promotes Cytokinesis in C. elegans by a CUL-3-Independent Mechanism. Curr. Biol. 15: 1605-15. Yang, H. Y., Mains, P.E. and McNally, F. J. (2005) Kinesin-1 mediates translocation of the meiotic spindle to the oocyte cortex through KCA-1, a novel cargo adapter. J. Cell Biol. 169: 447-457. Lu, C. and Mains, P.E. (2005) Mutations of a redundant α-tubulin gene affect C. elegans early embryonic cleavage via MEI-1/katanin dependent and independent pathways. Genetics 170: 115-26. Lu, C., Srayko, M. and Mains. P.E. (2004) Microtubule Severing Activity of the C. elegans MEI-1/MEI-2 Katanin Complex Prefers a Specific β-tubulin isotype, TBB-2. Molec. Biol. Cell 15: 142-150. Quintin, S., Mains, P.E., Zinke, A. and Hyman, A.A. (2003) mbk-2 kinase activity is required for degradation of MEI-1/Katanin in the one-cell C. elegans embryo. EMBO Report 4: 1173-1181. Piekny, A.J., Johnson, J.L.F., Cham, G.D. and Mains, P.E. (2003) The Caenorhabditis elegans nonmuscle myosin genes nmy-1 and nmy-2 function as redundant components of the let-502/Rho-binding kinase and mel-11/myosin phosphatase pathway during embryonic morphogenesis. Development 130: 5695-5704. Pintard, L., Willis, J.H., Willems, A., Johnson, J.L.F., Srayko, M., Kurz, T., Glaser, S., Mains, P.E., Tyers, M., Bowerman, B., and Peter, M. (2003) The BTB-containing protein MEL-26 is a core component of the CUL-3 ubiquitin-ligase and functions as a substrate specific adapter. Nature:425: 311-316.